The results of the PADN-HF-PH trial were announced at the ESC Congress 2026 and were simultaneously published in "The New England Journal of Medicine (NEJM)". The article in "NEJM" has as corresponding co-authors Professor Shao-Liang Chen from the First Hospital of Nanjing, academic Yaling Han from the General Hospital of the Northern Theater Command, and Professor Gregg W. Stone from Mount Sinai Hospital. This long-awaited publication represents a milestone in the field of cardiovascular interventions by providing high-quality clinical evidence that guides the next generation of global evidence-based therapeutic strategies for the management of heart failure.
The PADN-HF-PH trial is a multicenter, randomized, controlled clinical study that included 264 patients and was led by academic Yaling Han from the General Hospital of the Northern Theater Command. The objective of the trial was to analyze the safety and clinical efficacy of adding pulmonary artery denervation (PADN) to guideline-directed medical therapy (GDMT) in patients with pulmonary hypertension associated with left heart disease (PH-LHD).
In this type of patients, pulmonary hypertension and left heart pathology mutually exacerbate each other, resulting in a greater symptomatic burden and worse clinical outcomes. In current practice, therapies for PH-LHD mainly focus on the underlying left heart disease. Although GDMT improves the overall prognosis of those suffering from heart failure, there remains a significant lack of approved specific treatments directly targeting pulmonary hypertension.
Reduction of clinical worsening and recurrent events
During a mean follow-up of 338 days, the estimated 2-year incidence of clinical worsening according to the Kaplan-Meier method was 25.7% in the PADN plus GDMT group, compared to 51.5% in the group treated only with GDMT. This translates to a 51% reduction in the risk of clinical worsening (hazard ratio, 0.49; 95% confidence interval, 0.30 to 0.82; p = 0.006), an effect that remained stable throughout the entire follow-up period, a highly relevant aspect in a chronic and progressive disease.
The main assessment criterion was a demanding composite of clinical worsening events, which included death, heart or lung transplant, hospitalization for heart failure, outpatient worsening of heart failure requiring intravenous diuresis, or a significant reduction in the distance covered in the 6-minute walk test. This comprehensive approach allows for a more accurate capture of the long-term evolution of the disease state in these patients.
Regarding initial and recurrent clinical worsening events, the annualized rate was 36.3 per 100 patient-years in the PADN group, compared to 56.3 per 100 patient-years in the GDMT group. This represents a 35.5% reduction in the annualized rate of recurrent events (hazard ratio, 0.59; 95% CI, 0.39 to 0.89), indicating that PADN reduces the overall burden of the disease rather than merely postponing the first event.
Functional improvement, quality of life, and biomarkers
Treatment with PADN was associated with an improvement in functional capacity and health status. At 12 months, patients achieved a net improvement of 24.8 meters in the 6-minute walk test. In particular, the risk of experiencing a reduction of 10% or more in the distance covered in that test was reduced by 63% (hazard ratio: 0.37; 95% CI: 0.15 to 0.92).
The observed improvements in exercise capacity, health status, and ventricular function showed notable internal consistency. PADN translated into an improvement in health status assessed by the overall score of the Kansas City Cardiomyopathy Questionnaire (KCCQ-OSS). At 6 months post-procedure, patients showed a greater reduction in levels of natriuretic peptide (NT-proBNP) from baseline compared to those who received only GDMT.
Regarding safety, the procedure exhibited a favorable profile: bruising at the access site was recorded in only two patients in the PADN group and in one patient in the GDMT group, with no other complications attributable to the procedure observed.
The solid multidimensional evidence obtained in the PADN-HF-PH trial points to the creation of a new clinical paradigm. By globally reducing clinical worsening, decreasing the recurrence of events, and improving both functional status and key biomarkers, the study provides decisive data for the management of patients with pulmonary hypertension associated with left heart disease.
About pulmonary artery denervation
Pulmonary artery denervation (PADN), a technology patented by Pulnovo, is a minimally invasive therapy designed to modulate the hyperactivation of the sympathetic nervous system, which plays a relevant role in pulmonary vascular remodeling and in the progression of cardiopulmonary disease.
This technique has been recognized in several international clinical guidelines, including its inclusion as an experimental interventional therapy in the 2022 Guidelines of the European Society of Cardiology (ESC) / European Respiratory Society (ERS) for the diagnosis and treatment of pulmonary hypertension, and has been mentioned in a total of seven clinical guideline documents to date.
Clinical research on PADN continues in different subtypes of pulmonary hypertension. Following its regulatory approvals in 12 countries or regions and the experience accumulated in approximately 1,500 procedures in WHO Group 1 pulmonary hypertension, Pulnovo Medical is expanding the clinical development of this therapy to WHO Group 2 pulmonary hypertension associated with left heart disease (PH-LHD), with the aim of addressing the significant unmet clinical needs of a broader patient population.
About Pulnovo Medical
Pulnovo Medical is an innovative medical technology company focused on advancing interventional therapies for pulmonary hypertension and heart failure. Guided by clinical value, the company drives disruptive solutions based on its patented technological platform, with a clear commitment to global clinical development and commercialization, in order to improve patient outcomes worldwide. For more information, visit "www.pulnovomed.com".
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